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Biomedical subjects

E Whitehead

Publications and source records attributed to E Whitehead.

At least 19 recordsLinked to original sources

Adenosine deaminase from Saccharomyces cerevisiae: kinetics and interaction with transition and ground state inhibitors.

Several adenosine analogs, such as coformycin, 2'-deoxycoformycin and erythro-9-(3-nonyl-p-aminobenzyl)adenine (EHNA), which are strong inhibitors of mammalian adenosine deaminase, are much weaker inhibitors of the Saccharomyces cerevisiae enzyme. The specificity of the yeast enzyme is more restricted than that of mammalian adenosine deaminase, particularly towards the ribose moiety and around position 6 and 1 of the substrate. The sulphydryl group appears to be more masked in the yeast than in the mammalian enzyme. The kinetic effects of pH with adenosine substrate and with the inhibitor purine riboside are reported. The findings on specificity and pH kinetic effects can be interpreted in a model involving proton transfer from the -SH group of the enzyme to the N-1 atom of the substrate.

Adenine

Use of the carbon dioxide laser with the Montgomery T-tube in the management of extensive subglottic stenosis.

Subglottic and tracheal stenosis frequently present difficulties in management. Two cases of subglottic stenosis occurring after prolonged endotracheal intubation are presented where the vertical length of complete obstruction by scar tissue was greater than 2.5 cm. One case was successfully managed by the use of the laser and immediate insertion of a stent. The other case still requires subglottic stenting, although an excellent lumen was established by laser vaporization of the stenosed segment.

Adult

Simian T-cell leukemia virus type I infection in captive baboons.

Human T-cell leukemia virus type (HTLV-I) is a type C retrovirus that has been linked to both adult T-cell leukemia and neurological disorders in humans. Baboons and other Old World non-human primates harbor a related virus termed simian T-cell leukemia virus type 1 (STLV-I), which may also be associated with neoplastic disease. To explore the utility of the baboon as a model for HTLV-I infection and disease, 329 baboons from a colony of 3200 at the Southwest Foundation for Biomedical Research (SFBR) were analyzed for the presence of antibodies against STLV-I. An overall seroprevalence rate of > 40% was found, with higher rates in females versus males. Furthermore, seroprevalence rates increased dramatically with age, reaching greater than 80% in animals over the age of 16. Molecular and antigenic analysis of proviral DNA isolated from both tumor tissue and a cell line isolated from a baboon with non-Hodgkin's lymphoma (NHL) indicates that STLV-I in this colony is closely related to HTLV-I. Furthermore, monoclonally integrated provirus isolated from lymphoma tissue was detected, strongly implicating STLV-I in the etiology of this malignancy. DNA primer pairs homologous to HTLV-I sequences amplified both HTLV-I and STLV-I, but not HTLV-II, providing further evidence for a close genetic relationship between baboon-derived STLV-I and HTLV-I. The detailed study of a large population of naturally infected baboons may therefore shed some light into the complex processes required for the induction of disease associated with HTLV-I infection in humans.

Animals

A reverse-phase HPLC method for cAMP phosphodiesterase activity.

A simple and fast method based on reverse-phase HPLC has been developed for measuring the activity of cAMP phosphodiesterase. It allows quantitation of product and substrate in less than 10 min. The sensitivity (1*10(-11) mol AMP), the accurate evaluation of nucleotides, the unequivocal analysis of product, and the reproducibility of the system, make this method suitable for the evaluation of cAMP phosphodiesterase in biological material, at different levels of purification, and also in kinetic studies.

3',5'-Cyclic-AMP Phosphodiesterases

Experience with a subcutaneous implantable bone conduction hearing aid (Xomed Audiant) in a district general hospital.

Patients with a conductive hearing loss may find conventional hearing aids unsatisfactory for a variety of reasons. Efforts to overcome some of these difficulties have led to the development of the osteointegrated hearing aid. Implantable bone conduction hearing aids are an important advance in the treatment of well selected patients. Only 18 patients, who have been implanted with the Xomed Audiant bone conduction hearing aid, have so far been reported on in the UK. This report concerns a further six patients who have been implanted in one centre. Five of these patients continue to use their Audiant hearing aid 14 to 24 months after being fitted. They regard it to have significant advantages over their previous hearing aids. Four of the five patients use an ear level processor. Two of the patients who had previously used conventional bone conduction hearing aids now use the ear level processor.

Adolescent

A comparison of serum and saliva paracetamol concentrations.

The relationship between serum and saliva paracetamol concentrations was investigated in twenty healthy volunteers. The plasma and saliva drug concentrations showed a significant correlation (r = 0.67). However the agreement between the two methods of measurement was poor with limits of agreement of -15.3 mg l-1 to +15.9 mg l-1 with mean sample values of 19.2 and 19.5 mg l-1 for plasma and saliva, respectively.

Acetaminophen

A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers.

In this study we compared low (125 micrograms) and conventional (500 micrograms) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity. Following a two week placebo run-in period, 8 healthy male volunteers received 125 micrograms or 500 micrograms of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2. The 500 micrograms dose of cyclopenthiazide had a greater effect than the 125 micrograms dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II. Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers.

Adult

An open study of ropivacaine in extradural anaesthesia.

Ropivacaine 0.5%, 0.75% and 1.0% was investigated in an open study of extradural anaesthesia in three groups of 15 patients undergoing urological or orthopaedic surgery. Following a test dose of 3 ml of 1.0% lignocaine with 1:200,000 adrenaline, ropivacaine 20 ml was given in incremental doses over 4 min via a lumbar extradural catheter. The onset time for analgesia was short in all groups: T12 was blocked 4-6 min after the end of the injection of ropivacaine. The maximum segmental level was significantly higher in the 0.75% and the 1.0% groups (T2) than in the 0.5% group (T5). Complete motor block was obtained in seven, four and nine patients in the 0.5%, 0.75% and the 1.0% groups, respectively. Duration of analgesia increased with increasing concentration of ropivacaine: mean duration of analgesia was 203 and 266 min at T10 and 253 and 314 min at L5 for the 0.5 and 1% solutions, respectively. Mean duration of complete motor block was 94 and 192 min for the same solutions. Analgesia was satisfactory for surgery in all patients except for one in the 0.75% group. Hypotension was experienced by three, seven and three patients in the 0.5%, 0.75% and 1.0% groups, respectively. Bradycardia occurred in seven patients and was associated with hypotension in five. Backache was experienced after operation by four patients, and three patients complained of a brief mild headache. No late adverse events were seen.

Amides

Malignant melanoma of the larynx.

Malignant melanoma of the larynx is a rare tumour. Only 31 cases of primary laryngeal melanoma have been reported in the literature. Cady et al., (1968) found only four cases in a group of 2,500 cases of laryngeal cancer seen over a 25-year period. A case of primary malignant melanoma of the larynx is presented along with a review of the literature. Problems associated with histological diagnosis are discussed. This patient was regarded as a poor risk for laryngectomy and appears to have control of local disease following application of Carbon dioxide laser.

Aged

Vulnerability of the human Leydig cell to radiation damage is dependent upon age.

Testicular function was studied in three groups of patients previously treated for malignant disease, and a control group of adult males. The adult patients in groups one and two underwent unilateral orchidectomy for a testicular tumour but only in group two was this followed by post-operative high-dose irradiation (30 Gy) to the remaining testis. Four of the five boys in group three had a unilateral orchidectomy between the ages of 1 and 4 years and all five received a similar dose of irradiation (27.5-30 Gy) to the scrotum as in group two. The five subjects in group three were studied between the ages of 12 and 34 years. In group one the median basal testosterone level (16.0 nmol/l) was normal and the basal gonadotrophin levels mildly but significantly increased, reflecting a resetting of the pituitary-testicular axis following unilateral orchidectomy. In group two the median basal testosterone level (12.5 nmol/l) was significantly lower and the median basal FSH and LH levels were significantly higher than the respective values in group one, indicating that irradiation to the testis in adult life may damage both the germinal epithelium and the Leydig cells. All five males in group three showed grossly increased FSH and LH levels, with a median basal testosterone level (less than 2.5 nmol/l) significantly lower than groups one and two. None of the five showed a testosterone response to a stimulation test with human chorionic gonadotrophin or underwent puberty spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The pituitary-Leydig cell axis in men with severe damage to the germinal epithelium.

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The kinetics of ATP-dependent exonuclease V from Micrococcus lysodeikticus. A Michaelian dependence on DNA concentration.

The ATP-dependent exonuclease V from Micrococcus lysodekticus shows a Michaelian relation between steady-state velocity and the concentration of T7 DNA substrate. The Km (expressed as a mass concentration) does not change when the T7 DNA is broken into smaller fragments by a restriction enzyme. This is interpreted to mean that the predominant process by which the exonuclease-V--DNA complex breaks down is digestion of the entire DNA molecule rather than physical dissociation, in accord with the already known processive nature of degradation by this enzyme. The way that the V and Km towards DNA vary with ATP and ADP concentration suggests that enzyme-DNA complex is predominantly formed by reaction of DNA with an enzyme-ATP complex rather than with bare enzyme.

Adenosine Diphosphate

Hyaluronic acid in supragingival dental calculus.

A method is described for the isolation of heteropolysaccharides from human supragingival calculus. One component was identified as hyaluronic acid, by electrophoretic mobility, testicular hyaluronidase digestion and cetylpyridinium chloride profiles. No sulphated glycosaminoglycans were detected.

Dental Calculus

Use of high-dosage trimethoprim-sulfamethoxazole in sinusitis.

The combination trimethoprim-sulfamethoxazole was given in high dosage (four tablets twice daily) for either 2 or 5 days to 20 patients with sinusitis diagnosed on clinical grounds. In 11 the infection was improved or cured. Swabs cultured from 18 patients of the series produced no growth in 8. The organisms most likely to be isolated are Hemophilus influenzae and Diplococcus pneumoniae.

Adolescent